Psoriasis and the risk of diabetes Psoriasis affects over 7 million people in the US (125 million people worldwide) and is the most common helper T-cell (Th)-1 and Th-17 mediated inflammatory disease in humans. Epidemiological studies indicate that psoriasis is associated with an increased risk for major cardiovascular (CV) events and premature death due to CV disease independent of traditional risk factors. Emerging data suggest that patients with psoriasis may also be at increased risk for developing diabetes as well. The chronic inflammatory pathways involved in the maintenance of psoriasis have been shown to promote insulin resistance in animal and human models of diabetes. Furthermore, psoriasis and diabetes share susceptibility genes (such as CDKAL1). These shared genetic and inflammatory pathways suggest biologic plausibility for an increased risk of diabetes in patients with psoriasis. However, it is not known how clinical aspects of psoriasis (such as body surface area of involvement, anatomic sites of involvement, etc) impact diabetes risk nor is it known if successful treatment of psoriasis will lower the risk of diabetes. We will address these key knowledge gaps by conducting new aims to ongoing NIH funded projects. First, we will determine the risk of diabetes in a large population-based cohort of 9000 patients with psoriasis called the incident health outcomes and psoriasis events (iHOPE) study, established by R01 HL089744. Second we will determine how clinical aspects of psoriasis are associated with prevalent diabetes in a United States multi-centered clinic-based cohort of 1800 extensively phenotyped patients with psoriasis, 200 of whom have prevalent diabetes. This cohort was derived from the Dermatology Clinical Effectiveness Research Network (DCERN) established by RC1 AR058204. Third, we will determine if treatment of psoriasis with a systemic TNF-inhibitor (adalimumab) improves novel biomarkers which predict future development of diabetes compared to skin targeted treatment (ultraviolet B phototherapy) or placebo. This new aim will be investigated in the ongoing Vascular Inflammation in Psoriasis (VIP) trial funded by R01 HL111293, which is designed to evaluate vascular inflammation and lipid metabolism outcomes. These projects leverage existing studies conducted by the applicant to develop highly significant and innovative aims which will: 1) provide added value to ongoing studies while aiding the applicant to develop new skills in epidemiological and translational research focusing on diabetes; 2) address an important problem by determining which patients with psoriasis are at highest risk for developing diabetes thus warranting preventive interventions already proven to reduce the risk of diabetes; 3) determine if a class of medicines (i.e., TNF inhibitors) which are commonly used across multiple inflammatory disease indications hold promise for diabetes prevention through the study of innovative biomarkers in a rigorous randomized controlled trial which may yield new clinical practice paradigms; and, 4) provide a diverse clinical research platform in which to mentor young physician scientists in patient oriented research and promote their successful transition to independence.